This research studies the mechanism of the isotype-specific suppression mediated by the T cells with Fc receptors found in mice with myeloma. We have previously shown that mice and patients with myeloma develop an increase in T cells with surface-membrane Fc receptors (Immunol. Rev. 1981 56:115, J. Clin. Invest. 1981 67:308). Recently, we have found that the T cells with IgA-Fc receptors in IgA myeloma are isotype-specific suppressor cells (J. Immunol. 1983, 130:521). We, herein, propose to utilize normal immune response models to study the effects of T cells with IgA-Fc receptors (T-alpha cells) isolated from mice with IgA myeloma on: (1)\the immunoglobulin isotype switch from mu to alpha; (2)\the clonal expansion of IgA-committed B cells; (3)\the differentiation of IgA committed B cells to secretory plasma cells; (4)\the secretion of IgA plasma cells, and (5)\their effects on other immunoregulatory T cells. We also intend to utilize MOPC-315 as an IgA myeloma-tumor model to study the effects of T-alpha cells on: (1)\clonal growth of MOPC-315; (2)\MOPC-315 tumor cell survival; (3)\differentiation of MOPC-315; and (4)\immunoglobulin production and secretion by MOPC-315. We also intend to isolate and characterize any soluble-suppressor factors that are released by T-alpha cells found in mice with IgA myeloma cells. Finally, in order to confirm the generality of isotype-specific suppressor cell generation in myeloma, we will extend our studies of T-alpha cells and utilize similar models of normal immune responses and myeloma tumor models to study T-gamma cells in IgG myeloma and T-mu cells in IgM myeloma. The information generated from these studies is likely to: (1)\contribute further to our understanding of the host response to myeloma that may ultimately lead to the development of specific immunotherapeutic strategies for the treatment of myeloma and related disorders and (2)\contribute to our understanding of the regulation of isotype expression during normal immune responses. (LB)